Postnatal growth failure Causes, consequences and prevention Bielsko March 9, 2014 Ekhard E. Ziegler, M.D. Fomon Infant Nutrition Unit University of Iowa
1995; 26-29 weeks gestation
NICHD Growth Observational Study 2000 Extrauterine Growth Restriction 50th 10th 1500 Weight (grams) 1000 500 Intrauterine growth (50th and 10th percentile) 24-25 weeks 26-27 weeks 28-29 weeks 24 28 32 36 Ehrenkranz RA, et al. Pediatrics 1999;104:280-9. Postmenstrual Age (weeks) 3
Postnatal growth failure Significance Poor growth = Inadequate nutrition Inadequate nutrition = Impaired neurocognitive development Poor growth is a marker of poor neurocognitive outcome
McCance and Widdowson
Growth failure and neurodevelopmental outcome Ehrenkranz et al., Pediatrics 2006;117:1253 Setting: NICHD Neonatal Network Subjects: Infants born September 1994 and August 1995 with birth weight 500 1000 g (N=600 discharged) Outcomes: 1. Follow-up at 18-22 months (MDI, PDI, neurologic assessment (N=495) 2. Weight gain from regained birth weight to discharge
Growth failure and neuro-developmental outcome Ehrenkranz et al., Pediatrics 2006;117:1253 Q1 Q2 Q3 Q4 Weight gain (g/kg/d) 12.0 15.6 17.8 21.2 Head circ. gain (cm/week) 0.77 0.90 0.96 1.07 Cerebral palsy (%) 21 13 13 6 MDI <70 (%) 39 37 34 21 PDI <70 (%) 35 32 18 14 Neurodev. impairm. (%) 55 49 41 29
Postnatal growth failure and its association with poor neurocognitive outcome Birth year Age at FU Hack 1991 1977-79 8 yr Lucas 1998 1982-84 8 yr Weisglas-Kuperus 2009 1983 19 yr Latal-Hajnal 2003 1983-94 2 yr Georgieff 1985 1983 1 yr Kan et al. 2008 1991-92 8 yr Ehrenkranz 2006 1994-95 2 yr Franz 2009 1996-99 5 yr Claas 2011 1996-05 5.5 yr Belfort 2011 2001-06 2yr Rozé 2012 2003-08 2 yr
Slower vs faster growth Follow-up at 7.5-8 years of age Neurocognitive development Feeding Faster Slower p growth growth Average IQ 99.4 94.8 0.05 % with IQ <85 14 31 0.02 % with CP 1.5 12 0.03 % with IQ <85 and/or CP 15 38 0.003 Lucas et al., BMJ 317:1481 (1998)
VLBW infants (<1250 g), N= 219, z-scores for weight From Latal-Hajnal et al., J Pediat 2003;143:163
Extrauterine growth failure B. Latal-Hajnal et al., J Pediat 2003;143:163-70 MDI at age 2 yr AGA, no growth failure 101.7 SGA, catch-up 98.2 AGA, growth failure 94.9 SGA, no catch-up 94.7
Growth 1 Week to Term and 18-month Bayley scores Belfort et al., Pediatrics 2011;128:e899-e906 (Data from Australian DINO study [high-dose DHA] conducted by Makrides & Gibson 2001-2005; infants <33 wks) Points per 1 z-score increment MDI PDI All infants 2.4 (0.8-3.9) 2.7 ( 1.2-4.2) <1250 g 4.7 (2.1-7.4) 5.9 ( 3.2-8.6) >1250 g 1.0 (-0.8-2.8) 0.8 (-0.9-2.5) AGA 1.6 (0.0-3.3) 1.9 (0.3-3.5) SGA 11.7 (4.5-18.8) 11.2 (1.8-20.7)
Postnatal growth failure Is associated with poor neurocognitive outcome in dose-dependent fashion
Postnatal growth failure Definition 1. Falling off fetal growth trajectory 2. SGA status at 36 weeks PMA among infants born AGA Absence of growth failure: Parallel to fetal growth but 5% less
What degree of growth failure is free of adverse late effects? We cannot define any degree of growth failure that is OK
Postnatal growth failure Do we still have postnatal growth failure?
Henriksen et al. Br J Nutr 2009;102;1179-86 VLBW infants born 2003-2005
Infants born 2001-2010 23-25 wks Fenton et al. BMC Pediatr 2013;13:92
2010 4000 Weight (g) 3500 3000 2500 2000 1500 SGA AGA <27 weeks AGA 27-31 weeks Fenton 90th Fenton 50th Fenton 10th 1000 500 0 23 25 27 29 31 33 35 37 Gestational age (wks)
How does postnatal growth failure cause impaired neurodevelopment? It does not Growth failure and impaired neurodevelopment have the same cause Which is inadequate nutrition
Inadequate nutrition Growth failure Inadequate nutrition Impaired neurocognitive development
Does slow growth have positive effects? Slow growth may lead to more favorable cardiovascular health outcomes It definitely leads to bad neurocognitive outcomes Therefore, slow growth is unequivocally worse than faster growth Disadvantages clearly outweigh advantages
What is the primary cause of growth failure? When energy intakes are adequate, which they often are, inadequate protein intake is the most common cause of poor growth. The most common cause of inadequate protein intake is insufficient fortification of human milk
How do we know that extrauterine growth failure is due to inadequate nutrition? Nutrient intakes, especially protein intakes, are lower than required for growth to match growth of the fetus
Protein and energy intakes (per kg body weight) Year N BW (GA) Age 4 weeks Age 6 weeks g Energy Protein Energy Protein Simmer Aus 92-94 90 <2078 109 2.5 114 2.7 Carlson US 95 39 <1300 97 2.6 103 2.7 Olsen US 94-96 564 <1500 102 2.5 - - Radmacher US 97-00 220 <1000 98 2.8 108 2.9 Regan NZ 98 37 <32 wk 108 2.3 149 3.0 Embleton UK 99 38 <1750 121 3.1 - - Carlson US 01 46 <1000 107 3.1 116 3.2 Cormack NZ 03-04 34 <1790 140 2.8 - - Carlson US 06 68 <1000 110 3.3 118 3.4
The Factorial Approach 1. Fetal accretion 2. Inevitable losses 3. Efficiency of conversion 4. Efficiency of intestinal absorption
Protein requirement (Factorial method) Body weight 700-900 g Accretion* (g/d) 2.04 Dermal loss (g/d) 0.14 Urinary loss (g/d) 0.79 Required absorbed (g/d) 2.97 Required enteral intake (g/d) 3.40 (g/kg/d) 4.0 (g/100 kcal) 3.7 * with allowance for efficiency of conversion (90%)
Protein and energy requirements of preterm infants (enteral) Body weight Protein Energy Prot/Energy (g) (g/kg/d) (kcal/kg/d) (g/100 kcal) 500-700 4.0 105 3.8 700-900 4.0 108 3.7 900-1200 4.0 119 3.4 1200-1500 3.9 125 3.1 1500-1800 3.6 128 2.8 1800-2200 3.4 131 2.6
Factorial approach Specific nutrients Weight: 500 1000 g, enteral requirements per kg/d Accretion Requirement Ca (mg) 102 184 P (mg) 66 126 Mg (mg) 2.8 6.9 Na (meq) 1.54 3.3 K (meq) 0.78 2.4 Cl (meq) 1.26 2.8
Recommended Intakes ESPGHAN 2010* Protein g/kg/d g/100 kcal Weight <1000g 4.0-4.5 3.6-4.1 Weight 1000-1800 g 3.5-4.0 3.2-3.6 Energy *J Pediat Gast Nut 2010;50:85-91 110-135 kcal/kg/d
Postnatal growth failure The main cause is inadequate fortification of human milk
The apparent breastfeeding paradox in very preterm infants. Rozé et al., BMJ Open 2012;2:e000834 Breast feeding was associated with an increased risk of losing 1 weight Z-score during hospitalization Adjusted OR EPIPAGE 1.55 (1.14 2.12) 0.006 LIFT 2.51 (1.87 3.35) 0.001 p
At 5 years Rozé J et al. BMJ Open 2012;2:e000834
Postnatal growth failure Conclusion We may ever be able to eradicate postnatal growth failure In the meantime we must try Every improvement in nutrition will improve growth and may improve neurocognitive outcome